This study suggests that a combination of tests analysing DNA, RNA and protein changes in tumours could represent the best approach for obtaining molecular information that would be useful to oncologists in routine clinical practice for guiding them towards alternative treatments.
Jean-François Laes from the OncoDNA SA, in Rue Louis Breguet, Gosselies, Belgium said "Further research is required, including the screening of more cancer types and prospective studies into the use and the clinical utility of this type of information to inform subsequent treatment; the questions of how to best treat patients with currently available treatments, how to encourage clinical trial participation, and how to address the issue of drug cost and reimbursement are yet unanswered."
This has been successfully demonstrated for a number of therapeutics targeting the protein products of specific genes that are altered in human solid cancers, such as Erb-B2 Receptor Tyrosine Kinase 2 for trastuzumab, B-Raf Proto-Oncogene, Serine/Threonine Kinase for vemurafenib and dabrafenib, epidermal growth factor receptor for EGFR tyrosine kinase inhibitors or anti-EGFR antibodies, O-6-Methylguanine-DNA Methyltransferase promoter methylation status for temozolomide and, more recently, the expression of programmed death ligand 1 for anti-PD1 or anti-PD-L1 therapies in some solid tumours.
Figure 1: Variants identified by NGS. All the variants were stratified by potential functional impact and by cancer type.
In addition to approved therapies, off-label indications and drugs being investigated in clinical trials can be used for treatment if there is knowledge of alterations in genes and protein expression that would drive the development and survival of the tumour.
The nature and functional effect of mutations and unusual protein expressions are unique to the cancer type and specific to its tumour microenvironment, it is critical to provide the most comprehensive overview of all this information in each patient?s cancer.
An important point to highlight here is that the necessity of identifying these polymorphisms is not only to determine the real driver mutations, but also for the use of those passenger mutations as surrogates for tumour monitoring through liquid biopsy; many tests are exclusively focussed on sequencing but the expression of some proteins or the presence of some specific biomarkers could be valuable in defining which strategy to implement and in assisting oncologists in making treatment decisions; there is uncertainty surrounding whether the receipt of such a complex report influences the oncologists treatment decisions, and whether such testing ultimately helps patients.
The Laesresearch team concluded "Our study demonstrates that the combination of NGS and IHC/other tests provides the most useful information in aiding treatment decisions by oncologists in routine clinical practice."
Full text - https://doi.org/10.18632/oncotarget.24757
Correspondence to - Jean-François Laes - [email protected]
Keywords - molecular profiling, solid tumour, precision medicine, next-generation sequencing, therapeutic decision making in oncology
